Dysfunction of the GI innervation appears to be involved in a variety of debilitating diseases involving abnormal secretion, motility and inflammation in GI structures. In addition, the GI innervation is an important participant in the control of food intake and body weight. There is abundant evidence that sensory neurons in the vagus nerve respond to chemical changes in the lumen of the gut, including changes in specific nutrient content of the food. This nutrient responsiveness permits the brain to alter GI function and control food intake according to nutrient content in the gut lumen. In addition it is known that the intestinal wall contains about ten million enteric neurons, providing local control of gut function. Recent results suggest that certain peptides, may be released from enteric neurons, to activate vagal sensory nerves. However, there have been no efforts to identify the structural or chemical nature of connections between enteric neurons and vagal sensory neurons. Furthermore, nutrient responsiveness of enteric neurons is based on circumstantial evidence. Electrical responses to nutrients have not yet been recorded in enteric neurons. Therefore, one aim of this work is to examine the intestine for histochemically specific synaptic contacts between enteric neurons and vagal sensory neurons. The second aim is to record, intracellularly, from enteric neurons to determine their sensitivity to intestinal nutrients. The results should point the way toward more selective means of intervention in certain GI diseases and control of appetite.